The process which begins with recognition of antigen by antigen-sensitive cells and culminates in an immune response by their progeny can only be understood if the nature and function of different subsets of lymphocytes and even of individual lymphocytes which participate in the response is appreciated. The generation of both humoral and cellular responses is a complex event involving several functional subclasses of lymphocytes, including helper T cells. The experiments in this proposal are designed to carefully investigate a number of parameters related to the interaction of helper T cells with other types of effector cells, in particular cytotoxic T cell precursors and antibody-forming cell precursors. In these studies helper T cells are defined as cells that are required for the differentiation of a precursor cell into an active cytotoxic or antibody forming cell in the presence of specific antigen. The overall objectives are to characterize the requirement, nature and specificity of helper T cells which interact with the cytotoxic precursors, to determine the relationship between helper T cells which interact with cytotoxic precursors and with B cells specific for histocompatibility antigens, and to examine qualitatively and quantitatively the interaction of different types of helper T cells, including antigen-specific and antigen-non specific helper cells, with B cell which respond to a single type of antigen. Functional subclasses of lymphocytes will be identified using antisera specific for alloantigens which are differentially expressed on subsets of these cells, and the activity of individual T or B lymphocytes will be characterized using limiting dilution analysis.